Is ANO3 p.Arg494del (c.1479_1481del) pathogenic?

ANO3 p.Arg494del (c.14791481del) is classified Uncertain significance in ANO3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-11). Very rare (popmax 8.65e-05%, nfe); Associated with dystonic disorder.

What condition is associated with ANO3 p.Arg494del (c.1479_1481del)?

ANO3 p.Arg494del (c.1479_1481del) is associated with dystonic disorder (ClinVar).

How common is ANO3 p.Arg494del (c.1479_1481del) in the general population?

ANO3 p.Arg494del (c.1479_1481del) is very rare (popmax 8.65e-05%, nfe) (gnomAD).

ANO3 p.Arg494del

c.1479_1481del · rs1565132933 · VCV566078

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.65e-05%, nfe)

Conditions

dystonic disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.3	GERP -1.8, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.65e-05% European (non-Finnish) · 1/1,156,610 alleles

Overall 7.08e-05% 1/1,412,274 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ANO3
Protein: p.Arg494del
Coding: c.1479_1481del
MANE Select: NM_031418
dbSNP: rs1565132933
Type: Deletion
Location: chr11:26598394 (GRCh38)
Gene constraint: LOEUF 0.911 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.30
Residue 494: a UniProt-annotated variant site (in dyt24)

Full ANO3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dystonic disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ANO3 p.Arg494= Likely benign ★ same residue
ANO3 c.1032+15_1032+16del Likely benign ★★ same condition
ANO3 c.1290-13del Benign ★★ same condition
ANO3 c.1290-14del Benign/Likely benign ★★ same condition
ANO3 c.1290-19del Benign ★★ same condition
ANO3 c.1290-7del Benign/Likely benign ★★ same condition
ANO3 p.Tyr900fs Uncertain significance ★ same condition
ANO3 c.1290-13_1290-10del Likely benign ★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ano3-p-arg494del (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown